We propose to conduct a case-control study to test the hypothesis that persons with low levels of selenium are at increased risk of developing cancer of the breast, lung, and large bowel. In addition we plan to quantify the relation between dietary intake of selenium and levels in blood, urine, and toenails in normal controls and persons with clinical selenium toxicity. Work in vitro and animal studies demonstrate that selenium supplements reduce the incidence of carcinogen-induced and spontaneous neoplasms. The human evidence is scanty, but areas with high levels of selenium in the soil or blood seem to have lower rates of cancer, and cancer patients generally tend to have lower levels of selenium. We will study incident cases of cancer and a random sample of general population controls. Selenium intake will be measured using instrumental neutron activation of toenail clippings and tap water samples from all subjects. The base for this study will be the Rapid City Regional Hospital in Rapid City, South Dakota, where individual selenium blood levels are among the highest in this country and variations between individuals is unusually large. With 388 incident cancer cases expected over the 2 1/2 year study period there will be greater than 90% power to detect a difference of 15% in selenium concentration in the nails between cases and controls for each of the three cancer sites studied. The relationship between dietary intake of selenium and tissue levels in humans is poorly understood, as is the intake which leads to toxicity. This information is important if use of selenium is contemplated as a cancer chemopreventive agent. To quantify the relation between selenium intake and concentration of selenium in blood, urine, and toenails, we will collect duplicate samples of all food ingested for two day periods every three months for one year on 24 controls and 12 persons with suspected clinical selenium toxicity.